Ischemia-reperfusion causes a restricted proteolytic modification of cardiac TnT in the heart. This proteolytic cleavage specifically removes the N-terminal modulating segment of TnT preserving the TnT core structure and function. To investigate whether the restricted proteolytic removal of the N-terminal segment of cardiac TnT is a post-translational regulation in response to ischemia reperfusion, the sponsor's lab has constructed transgenic mice over-expressing the N-terminal truncated cardiac TnT in the heart. Characterization of this mouse model would determine the functional significance of this proteolytic modification in the pathophysiology of ischemic heart disease. This postdoctoral training proposal focuses on biochemical and physiological characterizations of the transgenic mouse hearts. Ca(2+) regulation of myofibril actomyosin ATPase activity, cardiomyocyte contractility, and working heart function will be studied. By using the transgenic mouse heart as an integrated experimental system, the results will contribute to the understanding of cardiac muscle contraction and adaptation in ischemic heart disease. [unreadable] [unreadable] [unreadable]